POS1272 INDUCTION OF REGULATORY T CELLS AND EFFICACY OF LOW DOSE INTERLEUKIN-2 IN SYSTEMIC SCLEROSIS: INTERVENTIONAL OPEN-LABEL PHASE 1–PHASE 2A STUDY
Authors: F. Barde, R. Lorenzon, S. Riviere, P. Cacoub, M. Rosenzwajg, C. Cacciatore, A. Daguenel-Nguyen, O. Fain, D. Klatzmann, A. Mekinian
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic sclerosis (SSc) is a chronic autoimmune disease, with impaired immune response, increased fibrosis, and endothelial dysfunction. (1,2) Regulatory T cells (Tregs), which are essential to prevent autoimmunity, showed a decreased frequency and impaired function during SSc. (3,4) Low-dose interleukin-2 (ld-IL2) can expand and activate Tregs, but there are no data in SSc. <h3>Objectives</h3> We aimed to assess the in vivo biological efficacy of ld-IL2 on Tregs and its safety in patients with SSc. <h3>Methods</h3> We performed an interventional prospective, open-label phase I-IIa study in nine patients with SSc without severe organ involvement (eight patients with limited cutaneous subtype). This trial is a part of the TRANSREG study. All patients received 1 Million International Units (MIU)/day of IL-2 for five days, followed by fortnightly injections for 6 months. The primary endpoint was the change in the relative Tregs blood concentration identified as CD25hiCD127lo/−Foxp3+cells frequencies on day 8 among TCD4+ cells compared with baseline. Laboratory and clinical evaluations (modified Rodnan skin score (mRSS), Clinical Global Impression (CGI) activity and severity scale) were performed between day 8 and month 18. <h3>Results</h3> At day 8, the primary endpoint was reached with a 1.8(± 0.5) fold increase of Tregs levels among TCD4<sup>+</sup> lymphocytes (p= 0.008). Changes in concentration of effector T cells (Teffs) and BCD19<sup>+</sup> cells were not statistically significant at day 8 and during maintenance period until month 6. Patients' clinical assessments were stable throughout the follow-up with no modification on mRSS CGI activity and severity scale. Ld-IL2 was well tolerated, and no serious adverse events occurred. <h3>Conclusion</h3> Ld-IL2 at a dosage of 1 MIU/day for five consecutive days selectively activates and expands Tregs in SSc. Safety data were very encouraging. Phase II efficacy trials are needed to validate therapeutic potential of ld-IL2. <h3>References</h3> [1]Allanore Y, Simms R, Distler O, Trojanowska M, Pope J, Denton CP, et al. Systemic sclerosis. Nat Rev Dis Primer. 23 avr 2015;1:15002. [2]Denton CP, Khanna D. Systemic sclerosis. Lancet Lond Engl. 7 oct 2017;390(10103):1685‑99. [3]Frantz C, Auffray C, Avouac J, Allanore Y. Regulatory T Cells in Systemic Sclerosis. Front Immunol. 2018;9:2356. [4]Antiga E, Quaglino P, Bellandi S, Volpi W, Del Bianco E, Comessatti A, et al. Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea. Br J Dermatol. mai 2010;162(5):1056‑63. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> François BARDE: None declared, Roberta Lorenzon: None declared, Sebastien RIVIERE: None declared, Patrice cacoub Shareholder of: ILTOO Pharma, Michelle Rosenzwajg Shareholder of: ILTOO Pharma, Carlotta CACCIATORE: None declared, Anne Daguenel-Nguyen: None declared, olivier fain: None declared, David Klatzmann Shareholder of: ILTOO Pharma, Arsene Mekinian: None declared.